CONTRACT RESEARCH
Researching co-crystallisation chemistry for improved APIs
Co-crystal solid forms provide an efficient way to modify the physicochemical properties of organic molecules and offer great potential for improving the properties of APIs and other substances, according to Dr Joan Feixas of Enantia SL, a Spanish chemical CRO with a strong focus on asymmetric chemistry and co-crystallisation technologies.
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n December 2011, the FDA issued a draft guidance document ‘Guidance for Industry Regulatory Classification of Pharmaceutical Co-Crystals’ which provides applicants of new drug applications (NDAs) and abbreviated new drug applications (ANDAs) with the Center for Drug Evaluation and Research’s current thinking on the appropriate classification of co-crystal solid-state forms. The draft guidance also provides information about the data that should be submitted to support the appropriate classification of a co-crystal and the regulatory implications of the classification. Traditionally, pharmaceutical solid-state forms of an API are grouped as either polymorphs or salts, and applicable regulatory schemes for these solid-state forms are well-defined. Co-crystals, however, are distinguishable from these traditional pharmaceutical solid-state forms. Unlike polymorphs, which generally speaking contain only the API within the crystal lattice, co- crystals are composed of an API with a neutral guest compound conformer in the lattice. Unlike salts, where the components
are in an ionised state, a co-crystal’s components are in a neutral state although they do not interact covalently.. At present no regulatory paradigm exists governing co- crystal forms.
Pharmaceutical co-crystals have opened the opportunity for engineering solid-state forms designed to have tailored properties to enhance drug product bioavailability and stability, as well as enhance processability of the solid material inputs in drug product manufacture. Pharmaceutical co-crystals offer the advantage of generating a diverse array of solid-state forms, even for APIs that lack ionisable functional groups needed for salt formation. The FDA’s draft guidance provides the Agency’s current thinking on the appropriate classification of co-crystal solid-state forms, the data that should be submitted to support the classification, and the regulatory implications of such a classification. Co-crystal containing drug products are not considered to contain new APIs, but rather to contain a specifically designed formulation component that is expected to contribute to improved drug product performance.
Co-crystallisation services
One of the leading European providers of co-crystallisation services for new APIs is Spanish company Enantia, which
specialises in chemical research and
development, custom synthesis and crystal engineering. The company has
View of a co-crystal obtained by combination of an API with a pharmaceutical-acceptable co-former.
20 sp2 Inter-Active March/April 2012
developed a strong focus on asymmetric chemistry and co-crystallisation
technologies as part of its integrated chemistry services from initial research in medicinal chemistry or route scouting to all phases of chemical process R&D. So how did this emphasis on asymmetric chemistry and co-crystallisation technology come about? “Early on, Enantia’s founders spotted an increasing need in the field of general organic synthesis and in particular a need for asymmetric synthesis services and formed a company to combine expert science with an innovative business model to ensure a strong client-oriented focus and professional management,” says Dr Joan Feixas, Enantia’s sales & financial director. “This has led to Enantia being been seen by our clients as the partner of choice to combine cutting-edge technology with the highest quality service. Since the foundation of the company in 2003, Enantia has been steadily growing and posting profits every year.
“Enantia has a number of advantages over its competitors stemming from its world-class science, unique culture and business model. We are one of Europe’s leading experts in the fields of asymmetric synthesis and crystal engineering, and our business model allows for complete flexibility according to the client’s needs: that is, classical FTE, shared risk- projects and fee-for-success projects, where the customer only pays if the project is completed successfully. This enables Enantia to truly become a strategic partner for a range of fine chemical, pharmaceutical and biotech companies.”
Exploiting new technologies Feixas says the philosophy of the company has been to keep on top of new technologies, so when the first publications referring to crystallisation appeared, Enantia realised the potential this could have for the pharmaceutical and chemical industry and decided to explore it. As a result, Enantia is one of the few companies globally that holds expertise in the field, and is now able to offer
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